Figure - available from: Journal of Plant Growth Regulation
This content is subject to copyright. Terms and conditions apply.
Proposed binding modes of GA3 (a) and compound HTS05309 (b) to GID1A (2ZSH). Hydrophobic residues are labeled in green, electrostatic interactions are labeled in red, water molecules are labeled in blue, and unique residues ASP190 were labeled in black. The yellow-dotted lines indicate the hydrogen bonds, purple-dotted lines indicate π–π interactions, and black solid lines indicate π-cation (Color figure online)
Source publication
Plant growth retardants can enhance the lodging resistance of crops and prevent yield losses. In this study, we used the crystal structure of the gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1 (GID1) to aid the discovery of novel growth retardants. The Maybridge database was filtered based on multiple-screening analysis, including pharmacophor...
Citations
... The synthetic routes of target compounds y1-y20, y12a-y12k were outlined in Scheme 1. Briefly, the synthetic process of the title compounds consists of the amide condensation reaction and the Suzuki-Miyaura coupling reaction [34][35][36]. Initially, the carboxyl of the substituted carboxylic acid (compounds 1/7/8) was transformed into acid chloride (intermediates 2/9/10), which was conducive for the amide condensation reaction. ...
The co-administration of anticancer drugs and P-glycoprotein (P-gp) inhibitors was a treatment strategy to surmount multidrug resistance (MDR) in anticancer chemotherapy. In this study, novel phenylfuran-bisamide derivatives were designed as P-gp inhibitors based on target-based drug design, and 31 novel compounds were synthesized and screened on MCF-7/ADR cells. The result of bioassay revealed that compound y12d exhibited low cytotoxicity and promising MDR reversal activity (IC50 = 0.0320 μM, reversal fold = 1163.0), 3.64-fold better than third-generation P-gp inhibitor tariquidar (IC50 = 0.1165 μM, reversal fold = 319.3). The results of Western blot and rhodamine 123 accumulation verified that compound y12d exhibited excellent MDR reversal activity by inhibiting the efflux function of P-gp but not expression. Furthermore, molecular docking showed that compound y12d bound to target P-gp by forming the double H-bond interactions with residue Gln 725. These results suggest that compound y12d might be a potential MDR reveal agent acting as a P-gp inhibitor in clinical therapeutics, and provide insight into design strategy and skeleton optimization for the development of P-gp inhibitors.
... Dicotyledon A. thaliana (Columbia-0) and monocotyledon rice (Nihonbare) were selected as the model plants to explore the bioactivities of the designed compounds Wang et al. 2019). ...
It has previously been demonstrated that a thiourea derivative, namely 1-phenethyl-3-[3-(trifluoromethyl)phenyl]thiourea (Y21), exhibits high gibberellin-like activity. In this work, the influence of the alkyl chain length and various benzene ring substituents on the biological activity of Y21 was investigated. 1-Substituted 3-[3-(trifluoromethyl)phenyl]thiourea derivatives were designed, synthesized, and comprehensively evaluated. The biological activity analysis demonstrated that at a dose of 0.1 μM, compound S8, i.e., 1-(3-bromophenethyl)-3-[3-(trifluoromethyl)phenyl]thiourea), exhibited significantly higher promoting activity with respect to Arabidopsis thaliana hypocotyl elongation and rice germination than did gibberellin A3 (GA3) and Y21. Moreover, the physiological response of the A. thaliana mutant ga1-1 to treatment with S8 suggested that this compound possessed GA-like function. The molecular docking analysis indicated that S8 formed hydrogen bonding interactions with residues Phe238 and Ser191 of the gibberellin insensitive DWARF1 (GID1) receptor, which resulted in stronger binding with GID1 than Y21. The bioactivity of derivatives S1–S22 exhibited a clear negative monotonic association with the molecular docking-based score values. Overall, it was determined that S8 displayed excellent GA-like bioactivity and facilitated hypocotyl elongation and germination; therefore, it could be applied as a potential plant growth regulator.
... In order to explore the symptomology of plants treated with designed compounds and preliminary bioactivity of synthetic compounds, A. thaliana (Columbia-0, Col-0) was cultured and used as a model test plant. [28][29][30] Surface-sterilized seeds were sown onto 1/2 Murashige & Skoog (MS) culture medium, containing 0.8% agar, 1% sucrose and compounds with indicated concentration. Subsequently, the plates were placed in the illumination box after seeds were incubated at 4°C for three days under darkness. ...
BACKGROUND
Picolinate/picolinic acid compounds are an important class of synthetic auxin herbicides. To explore the herbicidal activity of 6‐pyrazolyl picolinate compounds, a series of 3‐chloro‐6‐pyrazolyl‐picolinate derivatives was designed and synthesized.
RESULTS
Twenty‐five 3‐chloro‐6‐pyrazolyl‐picolinate derivatives synthesized were tested for herbicidal activity and the IC50 value of compound c5 to the growth of Arabidopsis thaliana root was 27 times lower than that of the commercial herbicide clopyralid. Compound c5 displayed better post‐emergence herbicidal activity and broader (Picloram, Clopyralid, Aminopyralid) herbicidal spectrum at a dosage of 400 g ha⁻¹ in comparison with clopyralid; it also was safe to wheat and maize at this dosage. Arabidopsis thaliana phenotypes and expression of auxin‐response genes demonstrated that compound c5 might be a novel auxin‐type herbicide. Molecular docking analyses revealed that compound c5 had stronger binding ability to receptor AFB5 (auxin signaling F‐box protein 5) than clopyralid.
CONCLUSION
These 6‐pyrazolyl picolinate compounds could be used as potential lead structures for the discovery of a novel synthetic auxin herbicide. © 2021 Society of Chemical Industry
A proposed strategy to overcome multidrug resistance (MDR) of anticancer drugs in chemotherapy is to disable the efflux function of P-glycoprotein (P-gp). In this study, based on ring-merging and fragment-growing strategies, 105 novel benzo five-membered heterocycle derivatives were designed, synthesized, and screened. Exploration of the structure-activity relationship (SAR) led to the identification of d7 with low cytotoxicity and promising reversal activity to doxorubicin in MCF-7/ADR cells. Furthermore, the mechanism studies revealed that the reversal activity of d7 stemmed from the inhibition of P-gp efflux. Molecular docking further clarified the observed trends in SAR with d7 displaying potent affinity to P-gp. Additionally, coadministration of d7 with doxorubicin achieved stronger antitumor activity in a xenograft model than doxorubicin alone. These results suggest that d7 is a potential MDR reveal agent acting as a P-gp inhibitor and provides guidelines for the future development of new P-gp inhibitors.
Deeper and longer roots allow crops to survive and flourish, but our understanding of the plant growth regulators promoting root system establishment is limited. Here, we report that, a novel auxin receptor agonist, named K-10, had a remarkable promotive effect on root growth in both Arabidopsis thaliana and Oryza sativa through the enhancement of root-related signaling responses. Using computer-aided drug discovery approaches, we developed potent lead compound by screening artificial chemicals on the basis of the auxin receptor TIR1 (Transport Inhibitor Response 1), and a series of N-(benzo[d] [1,3] dioxol-5-yl)-2-(one-benzylthio) acetamides, K-1 to K-22, were designed and synthesized. The results of bioassay showed that K-10 exhibited an excellent root growth-promoting activity far exceeding that of NAA (1-naphthylacetic acid). A further morphological investigation of the auxin related mutants (yucQ, tir1) revealed that K-10 had auxin-like physiological functions and was recognized by TIR1, and K-10 significantly enhanced auxin response reporter’s (DR5:GUS) transcriptional activity. Consistently, transcriptome analysis showed that K-10 induced a common transcriptional response with auxin and down-regulated the expression of root growth-inhibiting genes. Further molecular docking analysis revealed that K-10 had a stronger binding ability with TIR1 than NAA. These results indicated that this class of derivatives could be a promising scaffold for the discovery and development of novel auxin receptor agonists, and the employment of K-10 may be effective for enhancing root growth and crop production.
